Ophthalmic formulations often comprise compounds that provide desirable properties to the formulation. When these formulations are instilled in the eye, the properties of such compounds can help prevent ophthalmic problems such as bioadhesion and the formation of friction-induced tissue damage, as well as encourage the natural healing and restoration of previously damaged tissues.
Formulations are typically developed with a target viscosity to ensure that they are comfortable for the user and do not cause undesirable side effects such as blurring. A suitable formulation viscosity can help ensure that an ophthalmic formulation used in dry eye disorders will relieve dry eye-associated symptoms and/or treat the underlying disorder. In drug delivery applications the viscosity of ophthalmic formulations may be chosen to ensure that a pharmaceutical agent carried in the formulation remains in the eye for a desired length of time. Given its criticality, the viscosity of ophthalmic formulations should remain as stable as possible over time.
The viscosity of formulations can be affected by storage conditions (e.g., environmental temperature, time of storage, ambient light, etc.). Also, ophthalmic formulations must be sterilized before use, and the sterilization process, particularly heat sterilization, can dramatically affect the viscosity of such formulations.
Ophthalmic formulations have been previously described that utilize galactomannan-borate systems. U.S. Pat. No. 6,403,609 to Asgharian, entitled “Ophthalmic compositions containing galactomannan polymers and borate,” describes such systems and is herein incorporated by reference in its entirety. The cross-linking of galactomannan and borate is responsible for the gel-forming behavior of the described formulations. Magnesium has been utilized in guar formulations to assist in the hydration of guar. See Vega-Cantu et al., “Effect of Magnesium and Iron on the Hydration and Hydrolysis of Guar Gum” Biomacromolecules, Vol. 7:441-445, 2006.